Acute Myopic Shift after a Single Dose of Acetazolamide: A Case Report and Review of the Literature.

We report the case of a 32-year-old male who presented with an acute myopic shift as a result of uveal effusion following a single administration of 250 mg acetazolamide. The drug was discontinued and following cycloplegia and topical steroid therapy, we observed progressive deepening of the anterior chamber, reopening of the iridocorneal angle, and complete resolution of the myopic shift after 5 days. A literature review since 1956 identified 23 cases, including ours, which developed a myopic shift after a median time of 24 h (3 - 24) following a median dose of 500 mg (125 - 1000) acetazolamide, with about a third complicated by angle closure ocular hypertension. This presumed idiosyncratic reaction can occur without prior drug exposure and independent of the phakic status. Treatment options include systematic drug withdrawal associated with cycloplegia, anti-glaucomatous agents, and/or corticosteroids. Full recovery is achieved within about 5 days (2 - 14). Given the widespread use of acetazolamide, awareness of this idiosyncratic reaction is crucial to avoid complications of acute angle-closure glaucoma.

Dural Venous Sinus Stent Placement Reduces Dosage Requirements for Carbonic Anhydrase Inhibitors in Patients with Idiopathic Intracranial Hypertension.

This retrospective single-center study evaluated the change in required dosage of acetazolamide and topiramate before and after dural venous sinus stent placement (VSSP) for idiopathic intracranial hypertension (IIH). Adults diagnosed with IIH who failed optimized medical management and were treated with VSSP were included. This study comprised 55 patients who underwent VSSP for the diagnosis of IIH. The median preprocedural dosage of acetazolamide and topiramate was 1,000 mg (range, 500-4,000 mg) and 100 mg (range, 0-200 mg), respectively, among patients able to tolerate the medications. The median postprocedural dosage of acetazolamide and topiramate was 375 mg (range, 0-4,000 mg), with a mean reduction of 52.9% (P = .001), and 0 mg (range, 0-200 mg), with a mean reduction of 45.9% (P = .005), respectively. Dural VSSP significantly reduced dosage requirements for acetazolamide and/or topiramate, potentially reducing the morbidity secondary to medication side effects.

Intravenous or Oral Acetazolamide for Treatment of Diuretic-Induced Alkalosis in Patients With Heart Failure.

BACKGROUND: Acetazolamide has been used for diuretic-induced metabolic alkalosis, but the preferred dose, route, and frequency of administration remain unknown. OBJECTIVE: The purpose of this study was to characterize dosing strategies and determine the effectiveness of intravenous (IV) and oral (PO) acetazolamide for patients with heart failure (HF) with diuretic-induced metabolic alkalosis. METHODS: This was a multicenter, retrospective cohort study comparing the use of IV versus PO acetazolamide in patients with HF receiving at least 120 mg of furosemide for the treatment of metabolic alkalosis (serum bicarbonate CO2 ≥32). The primary outcome was the change in CO2 on the first basic metabolic panel (BMP) within 24 hours of the first dose of acetazolamide. Secondary outcomes included laboratory outcomes, such as change in bicarbonate, chloride, and incidence of hyponatremia and hypokalemia. This study was approved by the local institutional review board. RESULTS: IV acetazolamide was given in 35 patients and PO acetazolamide was given in 35 patients. Patients in both groups were given a median of 500 mg of acetazolamide in the first 24 hours. For the primary outcome, there was a significant decrease in CO2 on the first BMP within 24 hours after patients received the IV acetazolamide (-2 [interquartile range, IQR: -2, 0] vs 0 [IQR: -3, 1], P = 0.047). There were no differences in secondary outcomes. CONCLUSION AND RELEVANCE: IV acetazolamide resulted in significantly decreased bicarbonate within 24 hours of administration. IV acetazolamide may be preferred to treat diuretic-induced metabolic alkalosis in patients with HF.

Intracranial Hypertension Associated With Testosterone Therapy In Female-To-Male Transgender Patients: A Case Report And Literature Review.

We highlight a case of intracranial hypertension secondary to exogenous testosterone in a female-to-male transgender patient and present a systematic review of similar cases. Our review identified 19 female-to-male transgender individuals with intracranial hypertension. The mean age was 24.2 years and most common presenting symptom was headache (78.9% of patients). The most frequently associated ocular symptoms were transient visual obscurations (42.1%) and blurred vision (21.1%). Onset of symptoms occurred concurrently with exogenous testosterone therapy in 89.5% of the patients. The most common treatments were acetazolamide (89.5%), topiramate (31.6%), and alteration in hormone regimen (21.1%); four cases required surgery. These findings aid clinicians treating intracranial hypertension in patients undergoing gender affirmation therapy in a conscientious, patient-centered manner.

Normal saline, the known but least-examined fluid therapy method for preventing heme-induced nephropathy in children with glucose 6 phosphate dehydrogenase deficiency: a randomized controlled clinical trial.

BACKGROUND: Glucose 6 phosphate dehydrogenase deficiency (G6PDd) is the most common enzyme deficiency in humans. Randomized clinical trials comparing the efficacy of different types of fluid therapy for prevention of acute kidney injury (AKI) following hemolysis in patients with G6PDd are lacking. The present study aimed to compare the efficacy of three different types of fluid administration, isotonic saline with or without acetazolamide versus bicarbonate solution in prevention of AKI among children with acute hemolysis due to G6PDd. METHODS: In this double-blind randomized controlled clinical trial, 120 infants and children with acute hemolysis due to G6PDd were randomly divided into three groups consisting of 40 participants in each group. Group A received normal saline. Group B received normal saline plus oral acetazolamide at a dose of 5 mg/kg/day, and group C received half saline plus 75 mEq/L sodium bicarbonate. The primary outcome of this study was the frequency of AKI among the different types of fluid administration. RESULTS: In this study, 72 (60%) patients were boys with the mean age and length of hospital stay of 3.9 ± 2.2 years and 54.4 ± 29.9 h, respectively. AKI as the primary outcome of this study occurred only in one patient in group C and the rate of AKI did not differ significantly among patients receiving different types of fluid resuscitation (P > 0.05). CONCLUSION: Normal saline was equivalent to fluids containing alkalinizing agents in preventing heme-induced nephropathy in patients with G6PDd. A higher resolution version of the Graphical abstract is available as Supplementary information.

Acetazolamide in Acute Decompensated Heart Failure with Volume Overload.

BACKGROUND: Whether acetazolamide, a carbonic anhydrase inhibitor that reduces proximal tubular sodium reabsorption, can improve the efficiency of loop diuretics, potentially leading to more and faster decongestion in patients with acute decompensated heart failure with volume overload, is unclear. METHODS: In this multicenter, parallel-group, double-blind, randomized, placebo-controlled trial, we assigned patients with acute decompensated heart failure, clinical signs of volume overload (i.e., edema, pleural effusion, or ascites), and an N-terminal pro-B-type natriuretic peptide level of more than 1000 pg per milliliter or a B-type natriuretic peptide level of more than 250 pg per milliliter to receive either intravenous acetazolamide (500 mg once daily) or placebo added to standardized intravenous loop diuretics (at a dose equivalent to twice the oral maintenance dose). Randomization was stratified according to the left ventricular ejection fraction (≤40% or >40%). The primary end point was successful decongestion, defined as the absence of signs of volume overload, within 3 days after randomization and without an indication for escalation of decongestive therapy. Secondary end points included a composite of death from any cause or rehospitalization for heart failure during 3 months of follow-up. Safety was also assessed. RESULTS: A total of 519 patients underwent randomization. Successful decongestion occurred in 108 of 256 patients (42.2%) in the acetazolamide group and in 79 of 259 (30.5%) in the placebo group (risk ratio, 1.46; 95% confidence interval [CI], 1.17 to 1.82; P<0.001). Death from any cause or rehospitalization for heart failure occurred in 76 of 256 patients (29.7%) in the acetazolamide group and in 72 of 259 patients (27.8%) in the placebo group (hazard ratio, 1.07; 95% CI, 0.78 to 1.48). Acetazolamide treatment was associated with higher cumulative urine output and natriuresis, findings consistent with better diuretic efficiency. The incidence of worsening kidney function, hypokalemia, hypotension, and adverse events was similar in the two groups. CONCLUSIONS: The addition of acetazolamide to loop diuretic therapy in patients with acute decompensated heart failure resulted in a greater incidence of successful decongestion. (Funded by the Belgian Health Care Knowledge Center; ADVOR ClinicalTrials.gov number, NCT03505788.).

Acetazolamide: Old drug, new evidence?

Acetazolamide is an old drug used as an antiepileptic agent, amongst other indications. The drug is seldom used, primarily due to perceived poor efficacy and adverse events. Acetazolamide acts as a noncompetitive inhibitor of carbonic anhydrase, of which there are several subtypes in humans. Acetazolamide causes an acidification of the intracellular and extracellular environments activating acid-sensing ion channels, and these may account for the anti-seizure effects of acetazolamide. Other potential mechanisms are modulation of neuroinflammation and attenuation of high-frequency oscillations. The overall effect increases the seizure threshold in critical structures such as the hippocampus. The evidence for its clinical efficacy was from 12 observational studies of 941 patients. The 50% responder rate was 49%, 20% of patients were rendered seizure-free, and 30% were noted to have had at least one adverse event. We conclude that the evidence from several observational studies may overestimate efficacy because they lack a comparator; hence, this drug would need further randomized placebo-controlled trials to assess effectiveness and harm.

Pediatric Intracranial Hypertension: A Spotlight on Imaging, the Idiopathic Intracranial Hypertension Treatment Trial, and COVID-19 Associated Cases.

Primary intracranial hypertension (PIH) is characterized by clinical signs of increased intracranial pressure, papilledema, elevated opening pressure, and absence of mass lesion, hydrocephalus, or meningeal enhancement on neuroimaging. Visual changes are a common presenting feature and if untreated there is risk of irreversible vision loss. There have been recent proposed changes to the criteria for PIH along with studies looking at the differences in imaging characteristics between adult and pediatric PIH. The presence of transverse sinus stenosis alone was highly sensitive and specific for pediatric PIH. The Idiopathic Intracranial Hypertension Treatment Trial was an adult, multicenter study that examined the use of acetazolamide and weight loss on the course of PIH. The study confirmed many previously held beliefs including the most common presenting symptom in PIH is headache. Most patients present with bilateral papilledema with 58.2% of patients having symmetric Frisen scale grading and within one grade in 92.8%. Although diplopia is a common reported symptom, very few have evidence of cranial nerve palsy. Male gender, high-grade papilledema, and decreased visual acuity at presentation are risk factors for treatment failure. Acetazolamide use is associated with mild metabolic acidosis. During acetazolamide treatment, monitoring for hypokalemia or aplastic anemia is not recommended. Monitoring transaminases in the titration phase of treatment should be considered due to a case of transaminitis and pancreatitis with elevated lipase. Newer case reports have also seen associations of secondary intracranial hypertension with concurrent COVID-19 infection and MIS-C.

Oral acetazolamide for intraocular pressure lowering: balancing efficacy and safety in ophthalmic practice.

Introduction: Systemic acetazolamide is an efficacious adjunct to topical therapy to lower intraocular pressure (IOP) in glaucomatous eyes. This article aims to provide a comprehensive review for how best to use the agent in ophthalmic practice.Areas covered: This article will review the history, mechanism of action, methods of observing efficacy, indications for IOP lowering, side effects, allergy information including discussion of limited cross-reactivity between antimicrobial and non-antimicrobial sulfonamides, formulations, dosing and monitoring of acetazolamide. To select articles for this review, an electronic search was conducted using the PubMed database and cross-referencing was conducted for relevant literature.Expert opinion: The benefits of oral carbonic anhydrase inhibitor therapy can outweigh the risks in many circumstances. It is important that eye care practitioners work together with a patient's primary care practitioner to monitor for and mitigate risks. Greater education is needed with regard to the allergy profile of these powerful agents. Though not often a first-line option, oral carbonic anhydrase inhibitors remain pivotal and play in important role in delivery of eye care.

Anuric Acute Kidney Injury Requiring Dialysis Following Acetazolamide Use for Cataract Surgery.

BACKGROUND Acetazolamide (ACTZ) is commonly used in the prevention and treatment of various clinical conditions, and anuric acute kidney injury (AKI) is one of its known life-threatening complications. CASE REPORT We hereby report the case of a middle-aged man known to have compensated heart failure and hypertension with previously normal kidney function, who received a total dose of 2250mg of ACTZ over 3 days after cataract surgery. One week after the operation, he presented with anuria and severe bilateral renal colic, as well as progressively worsening kidney function and metabolic profile, which eventually required hemodialysis prior to recovery. CONCLUSIONS The cause of the AKI was attributed to intra-tubular obstruction by ACTZ-induced crystalluria, which required discontinuing the offending agent and dialysis to correct the kidney functions.

Phenotypic characterization of PIGN-associated paroxysmal dyskinesia in Soft-coated wheaten terriers and preliminary response to acetazolamide therapy.

A hereditary movement disorder in Soft coated wheaten terriers (SCWT) has been associated with a mutation in PIGN which encodes an enzyme involved in synthesis of glycosylphosphatidylinositol (GPI). The objective of this study was to describe and classify the clinical phenotype and assess therapeutic response. Twenty-five SCWT and related dogs homozygous for PIGN:c.398C>T with paroxysmal dyskinesia were available for inclusion. Medical records and video recordings of 17 dogs were evaluated in a retrospective case series. Affected dogs had episodes of involuntary, hyperkinetic movements and dystonia. Median age of onset was 2.5 years. A typical episode consisted of rapid, irregular hyperflexion and extension of the pelvic limbs with some degree of truncal dystonia. A mild episode consisted of spontaneous flexion of one pelvic limb while walking which could resemble a lameness. Episodes lasted several minutes to several hours and occurred up to 10 times/day or more. They were not associated with exercise or fasting but were sometimes triggered by excitement or stress. Acetazolamide therapy improved nine of 11 dogs, in seven cases abolishing episodes. Five of 17 dogs treated with other agents had mild improvement with clonazepam (n = 2), levetiracetam (n = 1), or phenobarbital (n = 2). Paroxysmal dyskinesias must be differentiated from seizure disorders since they often respond to different therapies. The SCWT phenotype consisted predominantly of hyperkinesia, and can respond dramatically to acetazolamide. GPI anchors proteins to the cell surface including carbonic anhydrase IV which modulates synaptic pH in the brain. Altered activity of this enzyme may be the target of acetazolamide therapy.

Severe Metabolic Acidosis and Hyperammonemia Induced by the Concomitant Use of Acetazolamide and Aspirin in a Patient With Impaired Renal Function.

BACKGROUND: Acetazolamide is contraindicated in patients undergoing dialysis and should be used with caution in patients with chronic kidney disease (CKD). Here, we evaluate the effect of the concomitant use of aspirin by patient with CKD using acetazolamide. CASE REPORT: A 63-year-old man with CKD and multimorbidity presented at our Emergency Department (ED) with general weakness and dyspnea for 4 days. Work-up at the ED revealed severe metabolic acidosis and hyperammonemia, which were initially considered signs of sepsis due to an elevated C-reactive protein level and pyuria. However, subsequent blood work indicated hyperchloremic acidosis with low lactate levels. After reviewing his medical history, we suspected the concomitant use of acetazolamide and aspirin as the etiology. Weakness, acidosis, and hyperammonemia were resolved after the patient discontinued acetazolamide. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Severe acidosis can be life threatening. Acetazolamide is known for causing mild metabolic acidosis, except in patients with severely impaired renal function. Here, we present a patient with mildly impaired renal function and concomitant aspirin use who developed severe metabolic acidosis and hyperammonemia after being prescribed acetazolamide. Regardless of the severity of the disease, patients with CKD should avoid taking acetazolamide concomitantly with aspirin.

Drug reaction with eosinophilia and systemic symptoms syndrome secondary to acetazolamide associated with markedly elevated procalcitonin.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an important cause of multi-organ dysfunction and can mimic other disorders including sepsis. We describe a patient presenting with septic shock and accompanying high procalcitonin. Although initially treated empirically with antibiotics, the emergence of eosinophilia during the admission lead to a revised diagnosis of DRESS syndrome, presumed secondary to acetazolamide. This case highlights the importance of regular clinical assessment and re-evaluation is key in identifying emerging features such as eosinophilia, rash and organ dysfunction, which can secure the diagnosis. Furthermore, the case also highlights that acetazolamide may be a rare cause of DRESS syndrome.